Many Questions Remain in Deciphering, Preventing Atopic March

In a new review article, investigators outline the challenges to studying the disease, but also point to big data as an important tool moving forward.

The atopic march—the pattern in which atopic dermatitis (AD) develops in children and is later followed by food allergies, allergic rhinitis (AR) and allergic asthma (AA)—is a much discussed and widely prevalent concept.

However, the full systemic character of the march, and the methods of identifying children at risk, remain the subject of much research and debate.

In a new review article published in the journal Children, corresponding author Mitsuru Tsuge, MD, of Japan's Okayama University, and colleagues explored some of the latest research into atopic march, and laid out the next steps.

Much of the recent research has centered on the question of the role, if any, of oxidative stress in the atopic march. Tsuge and colleagues began by defining terms, noting that oxidative stress is characterized by an imbalance between reactive oxygen species (ROS) and the body’s ability to detoxify reactive intermediates or repair the resulting damage.

The authors noted that atopic march is believed to be a systemic disease, rather than one confined to the skin. In that light, there is strong reason to suspect oxidative stress could be involved.

“Because ROS promote tissue inflammation, barrier defects, and upregulation of genes encoding proinflammatory cytokines, oxidative stress likely contributes to the progression of atopic march,” they said.

Earlier research has appeared to confirm that hypothesis, which the authors said opens up the potential for therapeutic interventions.

“Reduction of oxidative burden on these children using a variety of nutritional and pharmacological approaches might hold promise for this purpose,” they wrote.

However, the authors added that before such a therapy could make it to the clinic, investigators would need to develop biomarkers to identify children at highest risk of atopic march.

On that topic, Tsuge and colleagues said it can be difficult to track atopic march from an epidemiological standpoint, given that eczema tends to become less common with age, and AA and AR tend to increase in prevalence with age. They wrote that existing studies have sought to categorize children by the timing and persistence (if any) of their symptoms. One recent study came up with 4 different trajectory groups, potentially raising the possibility that clinicians might one day be able to predict an individual patient’s likely march.

Still, the authors acknowledged that part of the difficulty in predicting trajectories exists in the fact that both genetic and environmental factors can influence the diseases of the atopic march.

“The phenotypic diversity and interrelationships of allergic diseases make it challenging to elucidate their trajectories and predict individual prognoses,” they said. “However, given the recent rapid increase in the prevalence of allergic diseases, systematizing the trajectory of allergic diseases in the light of phenotypes and research on genetic and environmental factors is a high priority.”

The authors said big data may be able to play an important role here.

Tsuge and coauthors closed by turning their attention to prevention, by reviewing various studies in the United Kingdom, Israel, Australia, Germany, and the United States that examined whether introducing allergenic foods such as eggs, milk and peanut at an earlier age can prevent food allergies.

There is some evidence that introducing foods commonly associated with allergies at an earlier age can prevent allergies; in the United States, the American Academy of Pediatrics introduced new guidelines to recommend the introduction of these foods to infants earlier in an effort to prevent food allergy. However, in other countries the findings are not universally promising, and thus additional research is warranted.

The authors concluded that future study should look more closely at the onset and progression of atopic march, using the latest in big data and other analytic methods.


Tsuge M, Ikeda M, Matsumoto N, Yorifuji T, Tsukahara H. Current insights into atopic march. Children (Basel). Published online November 19, 2021 doi:10.3390/children8111067

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